Copper metalloproteins comprise the primary oxidases, oxygenases and certain oxygen carriers in animals. Our long range goal is the elucidation of the chemistry, metabolism, and biosynthesis of copper metalloproteins, with emphasis on ceruloplasmin, the blue copper protein of vertebrate serum which is a molecular link between iron and copper metabolism. Specific experimental approaches include: (1) a reexamination of the molecular parameters and biological and enzymic activities of native, undegraded ceruloplasmin; (2) the molecular mechanism of iron mobilization by ceruloplasmin; (3) the mechanism of biosynthesis of ceruloplasmin and other copper proteins in liver and the effect of estrogens, transition metal ions, and other agents, both stimulatory and inhibitory, on the biosynthesis of copper proteins; (4) the copper transport function of ceruloplasmin and the use of its copper for the biosynthesis of cytochrome oxidase and other tissue cupro-proteins; and (5) the evolutionary biochemistry of the copper storage and transport proteins and the changes in metalloprotein metabolism during development and differentiation.